Jiang Yawen, McCombs Jeffrey S, Park Susie H
Department of Pharmaceutical and Health Economics, Leonard D. Schaeffer Center for Health Policy and Economics, School of Pharmacy, University of Southern California, USC Schaeffer Center, Verna and Peter Dauterive Hall (VPD), 635 Downey Way, Los Angeles, CA, 90089-3333, USA.
Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
CNS Drugs. 2017 Apr;31(4):319-326. doi: 10.1007/s40263-017-0421-4.
A recent large database analysis raised concerns of potential acute kidney injury (AKI) risk associated with antipsychotics. However, whether individual atypical and typical antipsychotics are associated with differential AKI risks has not been investigated.
The current study compared the risks of AKI and known causes of AKI associated with a broad range of atypical and typical antipsychotics.
This retrospective cohort analysis used January 2007-June 2013 US nationwide Humana claims data to define episodes of antipsychotic drug therapy for patients with schizophrenia and bipolar disorder. Study drugs were aripiprazole, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Study outcomes were hospitalizations with AKI, and known causes of AKI, i.e., hypotension, acute urinary retention, neuroleptic malignant syndrome/rhabdomyolysis, and pneumonia. AKI was the primary outcome of the study. Cox regressions using haloperidol as the baseline comparator were used to estimate the impact of alternative antipsychotics on the risks of study adverse events following the initiation of treatment. The Cox models controlled for treatment history, comorbidities, and concomitant drug use in the prior 6 months. They also controlled for patient demographics and dose of current treatment.
The overall incidence of AKI was 25.0 per 1000 person-years. According to our multivariate regression results, the risk of AKI was significantly increased in patients taking olanzapine [hazard ratio (HR) 1.344, 95% confidence interval (CI) 1.057-1.708], quetiapine (HR 1.350, 95% CI 1.082-1.685), and ziprasidone (HR 1.338, 95% CI 1.035-1.729) relative to haloperidol. Aripiprazole (HR 1.152, 95% CI 0.908-1.462) and risperidone (HR 1.147, 95% CI 0.923-1.426) had insignificantly higher risks of AKI compared with haloperidol, whereas fluphenazine (HR 0.729, 95% CI 0.483-1.102) had an insignificantly lower risk of AKI. When compared between drug classes, atypical antipsychotics had a significantly higher risk of AKI (HR 1.313, 95% CI 1.083-1.591) than typical antipsychotics.
Antipsychotics are associated with differential AKI risks, with several atypical antipsychotics having higher risks than haloperidol. However, the overall incidence of AKI was moderate, and AKI risk should only raise concern for clinicians with elderly patients or patients who are vulnerable to kidney disease.
最近一项大型数据库分析引发了人们对与抗精神病药物相关的潜在急性肾损伤（AKI）风险的担忧。然而，个体非典型和典型抗精神病药物是否与不同的AKI风险相关尚未得到研究。
本研究比较了与广泛的非典型和典型抗精神病药物相关的AKI风险以及已知的AKI病因。
这项回顾性队列分析使用2007年1月至2013年6月美国全国范围内Humana的理赔数据，来确定精神分裂症和双相情感障碍患者的抗精神病药物治疗疗程。研究药物为阿立哌唑、氟奋乃静、氟哌啶醇、奥氮平、喹硫平、利培酮和齐拉西酮。研究结局为因AKI住院以及已知的AKI病因，即低血压、急性尿潴留、抗精神病药物恶性综合征/横纹肌溶解症和肺炎。AKI是该研究的主要结局。以氟哌啶醇作为基线对照的Cox回归用于估计在开始治疗后替代抗精神病药物对研究不良事件风险的影响。Cox模型控制了治疗史、合并症以及前6个月的合并用药情况。它们还控制了患者人口统计学特征和当前治疗剂量。
AKI的总体发病率为每1000人年25.0例。根据我们的多变量回归结果，与氟哌啶醇相比，服用奥氮平（风险比[HR] 1.344，95%置信区间[CI] 1.057 - 1.708）、喹硫平（HR 1.350，95% CI 1.082 - 1.685）和齐拉西酮（HR 1.338，95% CI 1.035 - 1.729）的患者发生AKI的风险显著增加。与氟哌啶醇相比，阿立哌唑（HR 1.152，95% CI 0.908 - 1.462）和利培酮（HR 1.147，95% CI 0.923 - 1.426）发生AKI的风险虽有升高但无统计学意义，而氟奋乃静（HR 0.729，95% CI 0.483 - 1.102）发生AKI的风险稍有降低但无统计学意义。在药物类别之间进行比较时，非典型抗精神病药物发生AKI的风险（HR 1.313，95% CI 1.083 - 1.591）显著高于典型抗精神病药物。
抗精神病药物与不同的AKI风险相关，几种非典型抗精神病药物的风险高于氟哌啶醇。然而，AKI的总体发病率为中等水平，AKI风险仅应引起临床医生对老年患者或易患肾脏疾病患者的关注。
